The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

Transposon mutagenesis provides a direct selection for mutants and is an extremely powerful technique to analyze genetic functions in a variety of prokaryotes. Transposon mutagenesis of Mycobacterium tuberculosis has been limited in part because of the inefficiency of the delivery systems. This report describes the development of conditionally replicating shuttle phasmids from the mycobacteriophages D29 and TM4 that enable efficient delivery of transposons into both fast-and slow-growing mycobacteria. These shuttle phasmids consist of an Escherichia coli cosmid vector containing either a miniTn10(kan) or Tn5367 inserted into a nonessential region of the phage genome. Thermosensitive mutations were created in the mycobacteriophage genome that allow replication at 30°C but not at 37°C (

To evaluate risk factors for osteonecrosis in human immunodeficiency virus (HIV)-infected patients, demographic and clinical characteristics of case patients (n=17) and control patients (n=34) matched on initial clinic visit date, length of follow-up, and baseline CD4 cell count were compared. Case patients were more likely to have received corticosteroids (47.1% vs. 8.8%; matched odds ratio [OR], 13.1; 95% confidence interval [CI], 1.6-106), to have had an increase in CD4 cell count from nadir >0.050 x 10(9) cells/L (64.7% vs. 35.3%; OR, 4.9; 95% CI, 1.0-24), and to have had Pneumocystis carinii pneumonia (52.9% vs. 11.8%; OR, 7.6; 95% CI, 1.6-36). Use of protease inhibitors and history of other opportunistic infections did not significantly differ. In multivariate analysis, use of corticosteroids remained significantly associated with osteonecrosis, independently of HIV disease stage and protease inhibitor therapy. Corticosteroid use is an important risk factor for osteonecrosis, but its pathogenesis is likely multifactorial.